Holoxan 1 g powder for solution for injection 1 g vial No. 1

Pharmacological properties

Ifosfamide is an alkylating cytostatic agent of the oxazaphosphorine group, the antitumor activity of which is associated with the alkylation of nucleophilic centers, disruption of DNA synthesis and blocking of proliferation in the late s- and early g2-phase of mitosis. The drug is rapidly absorbed in the intestine and metabolized in the liver with the formation of the active metabolite - 4-hydroxyphosphamide. Ifosfamide and its metabolites are excreted mainly in the urine; the half-life is 4-8 hours.

Indication

Inoperable malignant tumors sensitive to ifosfamide are lung, kidney, pancreatic, ovarian, breast, cervical cancer, seminoma, soft tissue sarcoma, malignant lymphomas.

Application

The course dose of Holoxan is 250-300 mg/kg (10-12 g/m2). The drug is usually administered intravenously at 50-60 mg/kg per day (2-2.4 g/m2 per day) for 5 days, preferably in the morning. A repeated course of treatment can be carried out no earlier than after 4 weeks. The drug can also be administered by long-term (up to 24 hours) intravenous infusion at a dose of 5-8 g/m2. Other treatment regimens are also possible. Holoxan solution is used for intravenous administration at a concentration of no more than 4%. Ready-to-use solution can be stored for no more than 48 hours at a temperature not higher than 8 °C.

Contraindication

Hypersensitivity to ifosfamide, severe bone marrow hypoplasia, hypoproteinemia, impaired renal function and urodynamics, pregnancy.

Side effects

Possible nausea, vomiting, hair loss, bone marrow depression with leukopenia and thrombocytopenia, immunosuppression, cystitis, impaired function of the gonads, sometimes impaired kidney and liver function, reversible encephalopathy, hypersensitivity reactions, radiation sensitization.

Special instructions

During the entire course of treatment with the drug and for 3 months after its discontinuation, reliable methods of contraception should be used to prevent pregnancy.

The drug should be used only in combination with Uroprot. Holoxan is less toxic than Endoxan, so it is more suitable for use in pediatric oncology.

Before starting treatment, urodynamic disorders should be eliminated, existing foci of infection should be sanitized, and water and electrolyte balance disorders should be corrected. For timely detection of side effects, regular general clinical blood and urine tests and biochemical tests are recommended. Side effects of chemotherapy can be prevented or significantly reduced by prescribing antiemetics, in severe leukopenia - by transfusion of whole blood and leukocyte mass, administration of γ - globulin, preventive antibacterial and antifungal therapy. Cystitis prophylaxis is carried out by administering a sufficient amount of fluid, prescribing adequate doses of the uroprotector Uroprot, and, if necessary, saluretics. Caution should be exercised when treating patients with one kidney; Holoxan treatment can be started no earlier than 3 months after nephrectomy. Special monitoring of the condition of patients with brain metastases is necessary.

Interactions

Platinum drugs can significantly enhance the nephro, myelo- and neurotoxicity of ifosfamide. With simultaneous use, the drug potentiates the hypoglycemic effect of antidiabetic drugs. Allopurinol enhances myelosuppression caused by holoxan.

Storage conditions

At a temperature not exceeding 25 °C.